Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets

The accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of Tau protein is two characteristic brain pathologies in Alzheimer's disease (AD). However, the Aβ hypothesis has recently faced challenges due to the limited clinical efficacy of anti-Aβ antibodies, such as aducanumab and lecanemab.

This comprehensive review highlights recent advances and debates regarding the pathophysiology of Aβ peptides and plaques in AD, as well as their use as biomarkers and drug targets.

Aβ aggregation is primarily driven by an imbalance between its generation from amyloid precursor protein (APP) and its clearance from the brain, processes influenced by various risk factors. The toxicity of amyloid plaques is affected by the accumulation of different Aβ species with varying lengths and post-translational modifications of Aβ. Additionally, pathways including neuroinflammation, blood-brain barrier deterioration, autophagy and mitochondrial dysfunction, lipid raft changes, and oxidative stress have pivotal roles in AD. Therefore, a clear map of Aβ's upstream regulators and downstream effectors is crucial for developing effective diagnostics and treatments for AD.

Incorporating new research findings and ongoing debates surrounding the Aβ cascade hypothesis is crucial for improving early diagnosis and for guiding the development of effective treatments for AD.